This study will evaluate the safety and efficacy of a recombinant adeno-associated virus vector (rAAV2tYF-GRK1-RPGR) in patients with X-linked retinitis pigmentosa caused by RPGR mutations.
This protocol includes a non-randomized, open-label, Phase 1/2 study (HORIZON). Approximately 30 participants will be enrolled into the dose escalation study (HORIZON). Each participant will receive the study agent by subretinal injection in one eye on a single occasion. Enrollment will begin with the lowest dose and will proceed to higher doses only after review of safety data by a Data and Safety Monitoring Committee (DSMC). There are a total of 15 visits over approximately 36 months, and long-term follow-up evaluations annually at years 4 and 5.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
29
Adeno-associated virus vector expressing a human RPGR gene
Duke University
Durham, North Carolina, United States
Cincinnati Eye Institute
Cincinnati, Ohio, United States
Casey Eye Institute
Portland, Oregon, United States
Retina Foundation of the Southwest
Dallas, Texas, United States
Number and proportion of Adverse Events
Number and proportion of participants experiencing Grade 3 or higher local (ocular) or systemic treatment-emergent adverse events that occur during the 36 months after study agent administration; number and proportion of participants experiencing treatment-emergent AEs, including treatment-emergent serious AEs;
Time frame: Day 0 - Month 36
Number and proportion of participants experiencing abnormal clinically relevant hematology or clinical chemistry parameters.
Time frame: Day 0 - Month 36
Changes from baseline in visual function as measured by mesopic microperimetry in the treated eye compared to the untreated eye
Time frame: Day 0 - Month 36
Changes from baseline in visual acuity
Time frame: Day 0 - Month 36
Changes from baseline in retinal structure as assessed by spectral-domain optical coherence tomography (SD-OCT)
Time frame: Day 0 - Month 36
Changes from baseline in quality of life questionnaire responses
Time frame: Day 0 - Month 36
Change from baseline in visual function by light-adapted perimetry
Time frame: Day 0 - Month 36
Change from baseline in fundus imaging
Time frame: Day 0 - Month 36
Change from baseline in full-field light sensitivity threshold (FST)
Time frame: Day 0 - Month 36
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Changes from baseline in visual function by dark-adapted full field perimetry (for subjects treated peripherally)
Time frame: Day 0 - Month 36